Platelet-derived growth factor (PDGF) is a polypeptide hormone capable of initiating the healing process following craniofacial injury. PDGF is stored in platelet alpha granules and released upon platelet degranulation. This system is highly effective in delivering a potent growth factor to fibroblasts, bone and smooth muscle cells. PDGF stimulates several cellular events associated with craniofacial wound healing. These include chemotaxis, pinocytosis, mitosis, bone remodeling and the synthesis of glycosaminoglycans, proteoglycans, proteins and DNA. Currently little is known about the cellular origin of this mitogen. PDGF is isolated from human platelets in two molecular weight forms, each consisting of two distinct chains linked together by disulfide bonds. However, the apparent dimorphism and dimeric structure of PDGF may be an artifact of proteolytic events during the isolation procedure. The goals of this proposal are to determine if megakaryocytes produce PDGF, elucidate the pathways of PDGF synthesis and compare PDGF synthesized by cells in vitro with PDGF isolated from platelets. These studies should provide fundamental knowledge on a polypeptide hormone thought to be essential for the healing response to traumatic injury.